Otitis media is one of the largest public health problems of young children. Otitis media is thought to be a multifactorial condition that can result from a variety of inciting events. However, once initiated, otitis media often converges on a final common pathway of inflammation, effusion and tissue hyperplasia that in turn can produce temporary and even permanent hearing loss. Upon resolution of otitis media the hyperplastic middle ear mucosa can recover to a condition at or close to its original structure, although permanent changes including fibrosis and osteoneogenesis sometimes occur. In the previous period of support, we identified several growth factors that can contribute to mucosal hyperplasia. In the current application, we propose to study mechanisms that control tissue hyperplasia and recovery of normal mucosal structure during otitis media. We will identify intracellular pathways that are activated in middle ear cells by growth factors, and determine whether inhibition of these pathways can reduce tissue hyperplasia during otitis media. We also propose to identify pathways controlling cell loss during recovery of the middle ear mucosa. We will determine whether stimulation or inhibition of activity in these pathways affects recovery from otitis media. Concurrent with these studies we will evaluate changes in the phenotype of the bacterial strain used to induce otitis media, to explore the potential for these changes to influence middle ear responses.